60 International Journal of Pharmaceutical Sciences and Nanotechnology Volume 1 • Issue 1 • April - June 2008

Design and Evaluation of Ethyl Cellulose Sustained Release Matrix

Tablets of Theophylline
D.Nagaswamy Venkatesh*, S.Sangeetha, M.K.Samanta, S.Sankar, and B.Suresh
Dept of Pharmaceutics, JSS College Of Pharmacy, Ootacamund – 1, Tamil Nadu.

ABSTRACT: Ethyl cellulose matrix tablets were prepared for sustained delivery of theophylline, a
bronchodilator. A wet granulation technique was employed to prepare matrix tablets by utilizing drug and
different concentrations of polymer (10, 20, 30, 40 and 50% WIN) were included in the formulation containing
200 mg of theophylline. The prepared tablets were evaluated for various physicochemical parameters by
official procedures. The in vitro release study of matrix tablets were carried out in phosphate buffers pH 1.2
and 6.8 for 12 hours. The prepared matrix tablets were showed 68.74%, 67.14%, 65.17%, 62.46%, and
57.24% release over a period of 12 hours. To investigate the drug release mechanism, the release data were
fitted into exponential models such as Higuchi and Peppa’s. Analysis of drug release rate drug from the
matrix system indicated that the drug was released by anomalous diffusion obeying zero order kinetics.
KEY WORDS: Theophylline, Ethyl Cellulose, Matrix tablets, Higuchi and Peppa’s model.

Introduction Preparation of SR Matrix Tablets

Oral slow and sustained release drug delivery systems can
release their drug content with a controlled manner,
producing a desirable blood serum level, reducing drug
toxicity and improving patient compliance by prolonging
dosing intervals1-4. Matrix systems composed of polymers
and other excipients as vehicles for drug delivery are
extremely popular in controlling the release rate5. It is the
system which prolongs and control release of drugs that is
dissolved or dispersed6. Ethyl cellulose has been
successfully used for many years to sustain the release rate
of drugs7. Theophylline, and its derivatives have long been
used for their bronchodilator properties in the management
of asthma and chronic obstructive pulmonary disease
(COPD)8. This drug has a great variability in clearance
(elimination half life 3-4 hr, adults 6-12 hr) and also has a
narrow therapeutic range (7.5-20 µg/ml). Once or twice
daily administration of controlled release preparations in
patients with COPD is recommended and improves patient
compliance9. Hence, the objective of this work was to
investigate the release of theophylline from tablets
prepared with ethyl cellulose as matrix material.
Materials and Methods
Theophylline anhydrous was procured from Sigma, USA.
Ethyl cellulose (20 cps) and lactose were purchased from
S.D.Fine Chemicals, Mumbai. Magnesium stearate and
talc were obtained from Loba chemie Pvt Ltd, Mumbai.
All other ingredients used were of analytical grade.
Corresponding author: D. Nagaswamy Venkatesh
Dept of Pharmaceutics, JSS College of Pharmacy,
Ootacamund – 1, Tamil Nadu.
email: nagasamyvenkatesh@rediffmail.com
SR tablets of theophylline were prepared by using drug and
different polymer concentration (10, 20, 30, 40 and 50%)
by wet granulation technique as shown in Table 1. All the
ingredients were passed through sieve no 100. Required
quantities of drug, polymer and diluents were mixed
thoroughly and sufficient quantity of granulating agent
(isopropanol and water in the ratio of 3:1) was added to get
dough mass. The mass was sieved through 22/40 mesh and
dried at 50° for 2 hour. The dried granules retained on 40
mesh were mixed with 10% fines, 2% talc and 1%
magnesium stearate. Tablets were compressed using 10
mm flat faced punches on a rotary tablet press (Remek,
Ahmedabad) at an appropriate compression force with the
hardness of all tablets maintained between 5-6 kg/cm2.
Evaluation of granules
The angle of repose (è) was measured according to the
fixed funnel and free standing cone method10, which
indicates the flowability of granules. Loose bulk density
(LBD) and tapped bulk density (TBD) were measured
using the formula: LBD=weight of the powder/volume of
packing, TBD=weight of the powder/tapped volume of
packing. Compressibility of the granules (CI) was
calculated using the formula CI=TBD-LBD/TBD×100.
The physical properties of granules were shown in Table. 2.
Physical characteristics of fabricated matrix
Tablets
All prepared matrix tablets were evaluated for its
uniformity of weight, hardness, friability and thickness
according to official methods11 shown in Table 2.
 D. Nagaswamy Venkatesh et al. : Design and Evaluation of Ethyl Cellulose Sustained Release… 61

Table 1. Composition of theophylline SR matrix tablets.

Ingredients Formulation code

F1 F2 F3 F4 F5
Theophylline anhydrous 200 200 200 200 200
Ethyl Cellulose 50 100 150 200 250
Lactose 235 185 135 85 35
Talc 5 5 5 5 5
Magnesium stearate 10 10 10 10 10
Total weight 500 mg 500 mg 500 mg 500 mg 500 mg

Table 2. Evaluation data of granules and matrix tablets of theophylline.

Loose bulk
Tapped bulk Drug
Formulation density Compressibility Friability Hardness Thickness
density content 2
code (LBD) Index (%) (%) (kg/cm ) (mm)
(TBD) (g/ml) (%)
(g/ml)
F1 0.461±0.04 0.526±0.03 12.36±0.05 99.8±0.4 0.20 5.5±0.9 3.59±0.41
F2 0.473±0.05 0.535±0.04 11.59±0.04 99.5±0.9 0.23 5.3±1.1 3.65±0.47
F3 0.479±0.04 0.547±0.02 12.43±0.03 99.7±0.6 0.25 5.4±0.8 3.62±0.43
F4 0.510±0.02 0.574±0.04 11.15±0.06 101.2±0.5 0.22 5.5±0.7 3.61±0.42
F5 0.520±0.05 0.580±0.05 10.34±0.03 99.8±0.5 0.20 5.6±0.8 3.68±0.40

100

90

80

70
Cumulative percent release

60

50

40

30

20

10

0
0 2 4 6 8 10 12
Time (h)

Fig 1. Cumulative percentage of release of theophylline from the matrix tablets F1(♦), F2(■), F3(▲), F4(×) and
F5(●). Samples were withdrawn at different time intervals and theophylline was estimated by UV
spectrophotometer.
62 International Journal of Pharmaceutical Sciences and Nanotechnology Volume 1 • Issue 1 • April - June 2008

Estimation of drug content in matrix Tablets
Ten tablets from each formulation were powdered. To 500
mg of the powder, 100 ml of 0.1 N hydrochloric acid was
added and digested for 15 min at 60º C and filtered. The
filtrate was then suitably diluted with 0.1 N hydrochloric
acid and analyzed against a blank by spectrophotmetrically
at 275.5 nm using a Schimadzu double beam
spectrophotometer12.
In vitro release studies
In vitro drug release studies were carried out using tablet
dissolution test apparatus USP XXIII. The dissolution
medium consisted of 0.1 N hydrochloric acid (pH 1.2) for
first 2 hours and phosphate buffer (pH 6.8) for subsequent
10 hours. An amount of 900 ml of the dissolution fluids
were used at 37±1° C with a stirring speed of 70± 2 rpm.
Aliquots of 5 ml were withdrawn at predetermined time
intervals and an equivalent amount of fresh dissolution
media maintained at the same temperature was replaced.
The samples were analyzed by measuring the absorbance
at 275.5 nm by UV spectrophotometer.
Data Treatment
Experimental results were fitted according to the following
exponential equation13.
Mt/M8 = Ktn
where, Mt/M8 is the fractional solvent absorbed or drug
released at time ‘t’; ‘k’ denotes a constant incorporating
properties of the macromolecular polymeric system and ‘n’
is a kinetic constant which depends on and used to
characterize the transport mechanism. For example, n=0.45
for case I or Fickian diffusion, when n=1, which is
characterized by a square root of time dependence in both
the amount diffused and the penetrating diffusion from
portion n=0.89 for case II transport, which is completely
governed by the rate of polymer relaxation, exhibits a
linear time dependence in both the amount diffused and the
penetrating swelling portion, n=0.45<n<0.89 for
anomalous behavior or non-fickian transport, which
exhibits whenever the rates of fickian and polymer
relaxation are comparable.
Results and Discussion
The present investigation was undertaken to design,
formulate and evaluate theophylline matrix tablets for
sustained release dosage form. IR studies indicated good
compatibility between drug, polymer and excipients. The
granules of different formulation were evaluated for angle
of repose, loose bulk density, tapped bulk density and
compressibility index. The granules indicated good
flowability with the angle of repose values ranging from 25
to 27° according to fixed funnel method. The results of
loose bulk density, tapped bulk density and compressibility
index are shown in Table 2. The result of compressibility
index was between 10.34±0.05 to 12.43±0.03, which is
below 15%, indicating good to excellent flow properties.
All tablet formulations were subjected to various
evaluation parameters and the results obtained were within
the range (Table 3). The weight variation test indicates that
all the tablets were uniform with low standard deviation
values. The thickness and diameter values ranged from
3.59±0.041 to 3.68± 0.047 and 10.72±0.05 to 10.97±0.07
mm respectively. The hardness of all the tablets were
between 5.3±1.1 and 5.6±0.8 kg/cm2. The loss in total
weight in friability test was in the range of 0.20 to 0.25%.
The percentage drug content for different tablets
formulations were varied from 99.5% to 101.2% indicating
the uniformity in drug content as shown in Table 2. The
matrix tablets containing 10% ethyl cellulose released
68.74% of drug at the end of 12th hour study, whereas drug
release from tablets containing 20%, 30%, 40% and 50%
of ethyl cellulose were 67.14%, 65.17%, 62.46% and 57.24
respectively, at the end of 12th hour. An inverse
relationship was observed between concentration of
polymer and release rate of theophylline from the matrix
tablets. Upon model fitting analysis of matrix tablets,
Peppa’s model with ‘n’ values 0.8253 to 0.8860 and the
correlation coefficient ‘r’ were found to be in the range of
0.9701 to 0.9746. This indicates that the release of
theophylline from matrix tablet follow zero order kinetics
with anomalous diffusion (Table 3).

Table 3. In vitro release kinetics of theophylline SR Matrix tablets

Formulation code Higuchi Peppa’s

r n r
F1 0.9889 0.8253 0.9701
F2 0.9866 0.8468 0.9774
F3 0.9864 0.8572 0.9821
F4 0.9855 0.8703 0.9810
F5 0.9879 0.8860 0.9746
 D. Nagaswamy Venkatesh et al. : Design and Evaluation of Ethyl Cellulose Sustained Release…
Conclusion
Formulation and evaluation of SR matrix tablets containing
theophylline was found to be potential, cost effective and
satisfactory in vitro release studies. In turn, it may enable
to release the drug in a sustained manner for prolonged
time and thereby accompanying some of the benefits like
reduction in total dose, frequency of administration, dose
related side effects and better patient compliance.
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